Abuse liability and anti-addiction potential of the atypical ? opioid receptor agonist IBNtxA Opioid drugs are crucial medications to treat acute and chronic pain. However, they are commonly abused and therefore spur wide societal costs. Thus there is a need to develop new analgesics with reduced addiction liability and new treatments for opioid addiction. IBNtxA, a novel opioid drug that is believed to activate selected splice variants of the ? opioid receptor (MOR), is reported to have reduced side effect profiles compared to current opioid analgesics. In this proposal, we will evaluate the abuse liability and subjective properties of IBNtxA using two mouse models: conditioned place preference (CPP) and drug discrimination (DD). IBNtxA will be tested for its ability to alter morphine-mediated CPP and reinstatement of morphine CPP. These experiments will measure the subjective rewarding properties of IBNtxA, its abuse liability, and its potential as a treatment for opioid addiction. DD tests, comparing IBNtxA against classical opioid agonists, will determine whether IBNtxA produces morphine- like behavioral responses or whether its effects are distinct from current opioid ligands, representing a new biological target for medications development. These studies will provide a foundation for future studies with IBNtxA and structural analogues to determine the molecular mechanisms underlying IBNtxA?s more favorable side effect profile and the role of MOR splice variant signaling in the development and treatment of opioid addiction.